Bevacizumab in NF2-related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation

Background: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality. Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. Methods: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. Results: Sixty-one patients (59% male), median age 25 years (range, 10–57), were reviewed. Median follow-up was 23 months (range, 3–53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. Conclusion: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.

An analysis of bimanual actions in natural feeding of semi-wild chimpanzees

Objective The objective of the current study was to investigate the lateral dominance for a bimanually coordinated natural feeding behavior in semi-wild chimpanzees. Materials and Methods We investigated strychnos spp. fruit consumption behaviors in semi-wild chimpanzees as an ecologically comparable feeding behavior to those found in cerebral lateralization studies of non-primate species. Video recordings of thirty-three chimpanzees were assessed while they consumed hard-shelled strychnos fruits. We explored statistical and descriptive measures of hand dominance to highlight lateralized patterns. Results Statistical evaluation of feeding bouts revealed a group-level right-handed bias for bimanual coordinated feeding actions, however few individuals were statistically lateralized. Descriptive analyses revealed that the majority of individuals were lateralized and possessed a right-handed bias for strychnos feeding behavior. Discussion The results provide empirical evidence in supports of an early evolutionary delineation of function for the right and left hemispheres. The present findings suggest that great apes express an intermediate stage along the phylogenetic trajectory of human manual lateralization.

Modulation of a cytoskeletal calpain-like protein induces major transitions in trypanosome morphology

Individual eukaryotic microbes, such as the kinetoplastid parasite Trypanosoma brucei, have a defined size, shape, and form yet transition through life cycle stages, each having a distinct morphology. In questioning the structural processes involved in these transitions, we have identified a large calpain-like protein that contains numerous GM6 repeats (ClpGM6) involved in determining T. brucei cell shape, size, and form. ClpGM6 is a cytoskeletal protein located within the flagellum along the flagellar attachment zone (FAZ). Depletion of ClpGM6 in trypomastigote forms produces cells with long free flagella and a shorter FAZ, accompanied by repositioning of the basal body, the kinetoplast, Golgi, and flagellar pocket, reflecting an epimastigote-like morphology. Hence, major changes in microbial cell form can be achieved by simple modulation of one or a few proteins via coordinated association and positioning of membrane and cytoskeletal components.